Critical care explorations最新文献

Objectives: Physiologic subtypes of acute hypoxemic respiratory failure (AHRF) may confer a differential response to treatments, particularly therapeutic strategies that are specific to pulmonary organ failure. We sought to identify physiologic latent classes of sepsis-associated AHRF defined by respiratory mechanics, oxygenation, ventilation, and radiographic patterns of lung injury, and to determine the association between class membership and 30-day mortality.

Design: We performed latent class analysis of patients with AHRF newly requiring mechanical ventilation enrolled in a prospective cohort of patients with sepsis from 2011 to 2020. We used logistic regression adjusted for Acute Physiology and Chronic Health Evaluation to determine the association between class membership and 30-day mortality and examined the distribution of patients classified as "hyperinflammatory" by previously described biomarker-based subphenotyping paradigms.

Setting: Philadelphia, Pennsylvania, United States.

Patients: Eight hundred eighty-two patients.

Measurements and main results: We identified two physiologic latent classes. Class 1 (n = 390) was characterized by low static compliance and impaired ventilation when compared with class 2 (n = 432). Mortality at 30 days was higher in the more physiologically severe class 1 when compared with class 2 (adjusted risk difference 0.12, p < 0.001) despite a similar severity of sepsis. Class 1 also contained a higher proportion of female patients and patients with obesity.

Conclusions: We identified two physiologic latent classes of sepsis-associated AHRF. Relative to class 2, class 1 was distinguished by low compliance, impaired ventilation, and higher 30-day mortality independent of the severity of sepsis. The higher percentage of female patients and patients with obesity in class 1 suggests a potential role for body composition in class determination. Physiologic classes were not primarily determined by qualification for acute respiratory distress syndrome or previously described biomarker-based subphenotypes, suggesting a distinct physiologic "axis" of heterogeneity.

Objectives: Guidelines recommend hydrocortisone as an adjunctive treatment in septic shock, but the optimal dosing regimen is unknown. A national shortage of hydrocortisone in 2023 prompted a change in institutional practice for hydrocortisone administration from 50 mg every 6 hours to 100 mg every 12 hours in an effort to reduce waste and conserve vials, creating an opportunity to evaluate the comparative effectiveness of these two regimens. The primary efficacy outcome was time to shock resolution, and secondary outcomes evaluated in this study were mortality, renal replacement therapy (RRT), medication costs, and maximum vasopressor dose attained.

Design: Single-center, retrospective cohort study.

Setting: ICUs in a quaternary academic medical center.

Patients: Adult patients admitted to an ICU with septic shock, defined by mean arterial pressure less than 65 mm Hg despite adequate fluid resuscitation and need for vasopressor infusion, who were treated with hydrocortisone for shock between October 24, 2022, and October 12, 2023.

Interventions: Treatment with hydrocortisone 50 mg every 6 hours or 100 mg every 12 hours.

Measurements and main results: One hundred thirty-eight patients were included in this retrospective chart review from October 24, 2022, to October 12, 2023. Data for 61 patients in the 50 mg every 6 hours group and 77 patients in the 100 mg every 12 hours group were collected and analyzed. In adjusted competing risk models, hydrocortisone regimen was not associated with differences in time to shock resolution (sub-hazard ratio [sub-HR] 0.95 [95% CI, 0.59-1.54]), ICU mortality (sub-HR 1.59; 95% CI, 0.89-2.84), in-hospital mortality (1.35; 95% CI, 0.81-2.26), or time to RRT (sub-HR 1.01; 95% CI, 0.45-2.31). In addition, the hydrocortisone dose regimen was not associated with differences in maximum vasopressor dose attained (mean difference in norepinephrine equivalent, 0.16 µg/kg/min; 95% CI, -0.26 to 0.58 µg/kg/min). The less frequent dosing resulted in cost savings of $446.10 (95% CI, 253.95-638.25) per patient treated with the more intensive but less frequent hydrocortisone dosing regimen.

Conclusions: A less frequent hydrocortisone dosing regimen was not associated with differences in time to shock resolution. Studies of the comparative effectiveness of different corticosteroid dosing regimens for septic shock are needed.

Background: The management of refractory status epilepticus (SE) remains an area of low evidence with varying management strategies. Treatment in the ICU is often postponed due to potential complications from sedation, and it is unknown if its efficacy is superior to additional treatment attempts with IV anti-seizure medications (ASMs). The Fast Acute Sedation at Intensive Care vs. High-Dose IV Anti-Seizure Medication for Treatment of Non-Convulsive Status Epilepticus (FAST) trial aims to compare the efficacy of rapid sedation in the ICU vs. add-on high-dose IV ASM alone for the treatment of refractory SE.

Methods/results: This prospective, randomized, multicenter trial will enroll adult patients with non-convulsive status epilepticus (NCSE) who either meet current EEG criteria or have unambiguous NCSE with minor motor phenomena ("subtle SE") but without ongoing tonic-clonic seizures that are refractory to benzodiazepines and treatment with at least one second-line ASM. Patients will be randomized to receive either rapid deep sedation for 20 hours with propofol and eventually low-dose midazolam or additional high-dose IV anticonvulsant therapy (levetiracetam, valproate, fosphenytoin, lacosamide, or topiramate) in the intermediate care unit. The primary endpoint is treatment failure, either defined as NCSE on EEG 24 hours after randomization or persistent NCSE after 3 hours despite therapy on continuous EEG or clinically. Secondary endpoints include assessment of new-onset neurologic deficits and modified Rankin Scale at discharge, economic analyses, length of hospital stay, in-hospital infections, and survival. Evaluations will be performed at baseline, discharge, and 3, 6, 12, and 24 months. The target sample size is 116 patients; we expect to have to randomize about 140 patients to reach the required number of patients.

Conclusions: The FAST trial is the first randomized clinical trial to investigate refractory NCSE. Regardless of the outcome, the results of this trial protocol will provide new class 1 evidence for the treatment of NCSE and establish the standard of care for this patient population in the future.

Trial registration: EU CT: 2024-515507-18-00/clinicaltrials.gov: NCT05263674.

Objectives: To use 3D imaging modalities to obtain precise measurements of the proximal tibia in pediatric patients and assess the safety of current intraosseous needle lengths (15 and 25 mm).

Design: Retrospective descriptive study.

Setting: University of Minnesota and MHealth Fairview System, Minneapolis, MN.

Patients: Pediatric patients (≤ 16 yr) who underwent full-body positron emission tomography-CT or axial MRI scans of the lower extremities between January 2014 and December 2023.

Interventions: None.

Measurements and main results: A total of 912 scans were initially retrieved; 232 scans were excluded due to osseous diseases, tibial fractures, suboptimal scan quality, or soft-tissue abnormalities, leaving 680 scans for analysis. Scans were stratified into 1-year age groups. Measurements at the proximal tibia included soft-tissue thickness, cortical bone thickness, and medullary canal diameter. Other values, such as the pre-intraosseous space (sum of cortical thickness and soft-tissue depth) and total distance to deep cortex, were calculated. Simulated needle insertions demonstrated that 31.62% of the 15 mm needles were too shallow, failing to reach the medullary canal, whereas 34.85% of the 25 mm needles were too deep, both of which could cause severe complications. A cutoff analysis for needle size based on age rather than weight was also calculated. For the 15 mm needle, 95% CI was not found in any age range, and the highest confidence cutoff was for using the needle in the age range of 0-8 years (91.9%). The 25 mm needle had a 97.8% CI from ages 10-16.

Conclusions: The study reveals significant age-related variability in the proximal tibia's anatomical dimensions, suggesting that standard 15 and 25 mm intraosseous needles may not reliably achieve optimal placement in pediatric patients. Our findings indicate that the current intraosseous needles may not be as safe as previously thought and support the need to develop improved intraosseous needle designs to enhance safety and therapeutic effectiveness in pediatric emergency care.

Objective: To determine the impact of using dynamic measures of fluid responsiveness in guiding the resuscitation of adult patients with sepsis and septic shock.

Data source: We searched MEDLINE, Embase, and unpublished sources from inception to February 3, 2025.

Study selection: We included randomized controlled trials (RCTs) that evaluated the use of dynamic measures of fluid responsiveness to guide resuscitation compared with any other method in patients with sepsis and septic shock.

Data extraction: We collected data regarding study and patient characteristics, definitions of fluid responsiveness, modality for assessing fluid responsiveness, and outcome data. We performed a random-effects meta-analysis and rated the certainty of the evidence using the Grading of Recommendations Assessment, Development, and Evaluation framework.

Data synthesis: We included nine eligible RCTs (n = 698 patients). The use of dynamic measures of fluid responsiveness to guide IV fluid (IVF) administration of patients with septic shock probably reduces 28-day mortality (relative risk] 0.61; 95% CI, 0.42-0.90, moderate certainty), may reduce the risk of acute kidney injury (AKI) (RR 0.66; 95% CI, 0.44-0.98, low certainty), and cumulative fluid balance on day 3 (mean difference -1.57L; 95% CI, -2.44 L to -0.69 L, low certainty). The use of dynamic measures of fluid responsiveness has an uncertain effect on ICU mortality, ICU and hospital length of stay, need for and duration of mechanical ventilation, need for renal replacement therapy, vasoactive medication administration, duration of vasopressor use, and IVF administration on day 1.

Conclusions: In adult patients with sepsis and septic shock, using dynamic measures of fluid responsiveness may improve survival and reduce the risk of AKI. Future studies should evaluate the impact of this intervention on other important clinical outcomes and determine the comparative efficacy of specific modalities for assessing fluid responsiveness.

Importance: Physical therapy (PT) interventions for patients supported with extracorporeal membrane oxygenation (ECMO) is thought to help preserve independence, but the impact of PT frequency on ECMO recovery is not well understood.

Objectives: To explore the relationship between PT frequency and functional outcomes in patients supported with ECMO.

Design, setting, and participants: Retrospective, single-center study of patients supported with ECMO at a large volume ECMO referral center. Patients were grouped by PT frequency (high < 3 d, moderate 3-7 d, and low > 7 d between sessions).

Main outcomes and measures: The primary outcome was the final Activity Measure for Post-Acute Care (AM-PAC) "6-Clicks" Basic Mobility Score. For the subgroup of patients discharged alive, a multivariable logistic model was used to understand what affected a patient's odds of a final AM-PAC score greater than or equal to 18, indicating functional independence.

Results: One hundred forty-two subjects were included with a median age of 48 years (interquartile range, 35-58 yr). Patients received venovenous (55%, n = 78/142) or venoarterial (45%, n = 64/142) ECMO. Of the cohort, 61% (n = 86/142) were discharged alive. A final AM-PAC score of greater than or equal to 18 was seen in 30% of patients (n = 43/142) before discharge. High- and moderate-frequency groups were more likely to survive to hospital discharge (76%, n = 22/29 and 75%, n = 38/51 vs. 44%, n = 27/62; p = 0.001). Controlling for age, sex, PT frequency, and the number of PT sessions after ECMO, logistic regression showed the number of PT sessions on ECMO (odds ratio, 1.13; 95% CI, 1.02-1.28) significantly impacted the odds of a final AM-PAC score greater than or equal to 18.

Conclusions and relevance: In patients supported with ECMO, high- and moderate-frequency of PT and PT on ECMO were associated with improved functional outcomes at hospital discharge.

Objectives background: Monocyte anisocytosis (monocyte distribution width [MDW]) has been previously validated to predict sepsis and outcome in patients presenting in the emergency department and mixed-population ICUs. Determining sepsis in a critically ill surgical/trauma population is often difficult due to concomitant inflammation and stress. We examined whether MDW could identify sepsis among patients admitted to a surgical/trauma ICU and predict clinical outcome.

Design: Secondary analysis of three prospective observational clinical studies.

Setting: Single institution ICU.

Patients/subjects: Two hundred thirty-eight participants were included in this study: 107 patients who were admitted to the ICU and adjudicated to have sepsis, 80 patients who were considered critically ill nonseptic (CINS), and 51 healthy control participants.

Interventions: MDW was measured among hospitalized patients admitted to the ICU with the diagnosis of sepsis or CINS patients at risk of developing sepsis. Blood samples were collected at admission and at intervals during ICU admission.

Measurements and main results: MDW significantly differed between septic and CINS patients on ICU admission (26.4, interquartile range [IQR, 23.5-30.8] vs. 20.1 [IQR, 17.9-21.9]; p < 0.001) and could discriminate with an area under the receiver operating characteristic curve of 0.85 (95% CI, 0.79-0.91; p < 0.001). An MDW of greater than 22.0 at admission to the ICU could identify sepsis with a 78% specificity and a 90% sensitivity but could not discriminate in-hospital, 30-day, or 90-day mortality.

Limitations: Small sample size from a single institution. Our analysis did not include other relevant biomarkers such as procalcitonin, C-reactive protein, and interleukin-6. In the imputation of missing values, linear mixed-effect models were used, risking model misspecification and the violation of the missing-at-random assumption.

Conclusions: Among surgical/trauma ICU patients, MDW can discriminate between sepsis and nonseptic inflammation, but it is a weak predictor of mortality.

Importance: Sepsis remains a leading cause of death in infectious cases. The heterogeneity of immune responses is a major challenge in the management and prognostication of patients with sepsis. Identifying distinct immune response subphenotypes using parsimonious classifiers may improve outcome prediction, particularly in resource-limited settings.

Objectives: This study aimed to evaluate whether classification of the immune response can serve as a predictor of mortality.

Design, setting, and participants: This prospective cohort study was conducted in the emergency department, inpatient wards, and ICU of a tertiary hospital. Adult patients diagnosed with sepsis within the previous 24 hours were included. Exclusion criteria were history of RBC transfusion, major thalassemia, decompensated cirrhosis, hematologic malignancy, or use of immunosuppressive or chronic corticosteroid therapy. Demographic, clinical, and laboratory data-including serum ferritin and monocyte human leukocyte antigen-DR/Human Leukocyte Antigen-DR) (mHLA-DR) levels-were collected.

Main outcomes and measures: Subjects were classified into the following immune subphenotypes: macrophage activation-like syndrome (MALS) (if ferritin > 4420 ng/mL), immunoparalysis (if mHLA-DR < 10,000 receptors/cell and ferritin ≤ 4420 ng/mL), and unclassified (if they did not meet the criteria for either MALS or immunoparalysis). The primary outcome was in-hospital mortality.

Results: Of the 200 subjects recruited, 54 (27%) were classified into the MALS group, 19 (9.5%) into the immunoparalysis group, and the remainder into the unclassified group. The in-hospital mortality rates for the MALS, immune paralysis, and unclassified groups were 83.3%, 68.4%, and 51.1%, respectively. The proportional hazards assumption was met between the MALS and unclassified groups (crude hazard ratio [HR] 2.3; 95% CI, 1.56-3.35) but not between the immunoparalysis and unclassified groups (crude HR 1.4; 95% CI, 0.76-2.50). After adjusting for confounding variables, MALS's adjusted HR was 1.7 (95% CI, 1.13-2.49; p = 0.01).

Conclusions and relevance: The MALS subphenotype is an independent predictor of in-hospital mortality in sepsis.